Methods for using a pipetting device with independently movable pipette units

ABSTRACT

The invention provides for a method of pipetting samples using a pipetting device including more than one pipetting unit. Each of the pipetting units are independently movable in Y and Z directions and includes an upper and a lower frame. Two adjacent pipetting units include a module arranged in a staggered manner in either of the respective upper and lower frames.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a divisional of U.S. application Ser. No.13/169,593 filed on Jun. 27, 2011, U.S. Pat. No. 8,900,527, which claimsthe benefit of priority under 35 U.S.C. §119 of EP10167646.8, filed Jun.29, 2010, the contents of each are incorporated by reference herein intheir entirety.

FIELD OF THE INVENTION

The present invention relates to a pipetting device, method and systemwith more than one pipetting units, wherein said pipetting units aremovable relative to each other along one axis.

BACKGROUND OF THE INVENTION

Pipetting devices are used in automated analyzers for distributingsamples or reagents. Pipetting devices comprising more than onepipetting unit are known in the art. Movable pipetting units are usefulto transfer samples or reagents from one number of vessels to anothernumber of vessels. Such a device with movable pipetting units is knownfrom US2001/0036425.

The present invention provides an improved device with movable pipettingunits.

SUMMARY OF THE INVENTION

The present invention relates to a device for aspirating and dispensingmore than one liquid sample. The invention also relates to an analyzercomprising such a device. The device comprises a main frame body andmore than one pipetting units, said pipetting units extending side byside in parallel with each other. A pipetting unit comprises aninterface for interacting with an interface of a pipette tip. It furthercomprises a first module for aspirating and dispensing a liquid. Onepreferred embodiment of such a module is a pump (708). It furthercomprises a second module for Y-axis movement, and third module forZ-axis movement, wherein said second and third modules functionindependently. Said second and third modules are preferably actuators.More preferably, said third module is a spindle drive. Said pipette unitfurther comprises a fourth module for controlling functions of saidpipette unit. Preferably, said fourth module is an electronic modulecontrolling all functions of said pipette unit. The pipetting unitcomprises two frames for receiving at least one of said modules, whereinsaid at least one module is mounted in one of said frames. Furthermore,the device comprises an X-transfer mechanism (719) connected to saidmain frame body to which said pipetting units are connected. Said atleast one module of one pipette unit is mounted in one of said twoframes, and said at least one module of the adjacent pipette units aremounted in the frame in the location corresponding to the frame of saidfirst pipette unit which is empty.

The device according to the present invention has the advantage that anappropriate spacing between pipette units can be achieved even ifmodules required for each pipette unit are too broad to be placed nextto each other.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows two pipette units with staggered modules connected to aframe part.

FIG. 2 shows two pipette units moved into close proximity of each other.

FIG. 3 a) shows five pipette units connected to one frame part. Fourpipette units are in close proximity, the fifth pipette unit is movedindependently away from the others. In b) eight pipetting units areshown in close proximity to each other.

FIG. 4 a) shows a device with two units fixed to a support for movementin Z-direction, but not in Y-direction. b) shows the two units from a)with individual parts separated.

FIG. 5 a) shows the interface of frame parts with Y-carriage; b) adetail of the interacting part before engagement; c) the frame engagedto the frame body.

FIG. 6 shows an adapter plate (a) and the adapter plate with pipettingunit fixed to the frame part (b).

FIG. 7 shows examples of sensors: a) a magnet, a hallsensor, aninit-sensor of the Z-drive; b) an init sensor of the Y-drive; c) anultrasound sensor.

DETAILED DESCRIPTION OF THE INVENTION

In one embodiment of the device hereinbefore described, at least onemodule is mounted outside of said frame, wherein the said modules of twoadjacent pipetting units are staggered. This again allows achieving anappropriate spacing between said pipetting units. In another embodiment,the pipetting unit does not comprise frames. In this embodiment, atleast one module is mounted in a staggered fashion on two adjacentpipetting units.

A preferred shortest distance between said more than one pipette unitsis 10 mm or shorter. More preferably, the shortest distance between saidmore than one pipette units is between 10 mm and 1 mm. Further preferredshortest distances are 9 mm, 4.5 mm, 2.25 mm, and 1.125 mm.

In a preferred embodiment, the device hereinbefore describedadditionally comprises a sixth module, which is a sensor module.Preferred sensor modules are sensors for initializing or determining theposition in Y or Z direction of the pipette unit. Preferred sensors fordetermining the position of the pipette unit in is an ultrasound sensor.

Preferably, one side of a pipette unit is connected to said Y-axistransfer mechanism.

Preferably, said pipette units additionally comprise ball bearings,wherein said ball bearings of two adjacent pipette units are staggered.

The present invention further relates to a method of pipetting samplesfrom a first set of vessels holding said samples to a second set ofvessels, wherein the distance between adjacent vessels of the first setof vessels is different from the distance between adjacent vessels ofthe second set of vessels. Said method comprises aspirating said sampleswith pipette tips mounted on a device hereinbefore described, whereinthe distance between said pipetting units is adjusted to the distancebetween said first set of vessels by moving the pipetting units alongone axis prior to aspiration. The distance between the pipette units tothe distance between said second set of vessels prior to dispensing isthen adjusted for dispensing said samples into the second set ofvessels.

In a preferred embodiment of the method hereinbefore described, saidfirst set of vessels comprises at least two vessels in a lineararrangement. Preferably, said second set of vessels are integrallyformed. In another preferred embodiment, the second set of vessels isonly one vessel. In a more preferred embodiment, said second set ofvessels comprises a multiwell plate.

The present invention further relates to a method of isolating andanalyzing at least one analyte that may be present in at least oneliquid sample in an automated analytical system, comprising theautomated steps of providing a first set of vessels comprising said atleast one liquid sample to said automated analytical system; aspiratingat least a portion of said at least two liquid samples from said firstset of vessels with a pipetting device comprising more than onepipetting unit, wherein the distance between said pipetting units isadjusted to the distance between the first set of vessels prior toaspiration; adjusting the distance between said pipetting units to thedistance between vessels of a second set of vessels; dispensing saidliquid samples into said second set of vessels. The method furthercomprises the steps of combining together a solid support material andone of said fluid samples in a well of said second set of vessels vesselfor a period of time and under conditions sufficient to permit saidanalyte to be immobilized on the solid support material. Isolating thesolid support material is then isolated from other material present inthe fluid sample in a separation station. The analyte is then purifiedin the separation station by separating the fluid sample from the solidsupport material and washing the materials one or more times with a washbuffer. Finally, the analyte is analyzed. In a preferred embodiment, themethod comprises at least two liquid samples. In another preferredembodiment, said analyte is a nucleic acid. More preferably, said devicecomprises the device hereinbefore described.

The present invention also relates to an analytical system for isolatingan analyte, comprising a module for transferring samples from a firstset of vessels to a second set of vessels, wherein said module comprisesa pipetting device comprising more than one pipetting units, whereinsaid pipetting units are movable relative to each other along one axis;and a module for isolating said analyte. Preferably, said analyticalsystem additionally comprises a module for analyzing said analyte.

A device (700) according to the invention comprising a main frame body(701) and two pipetting units (702 a, b) is shown in FIG. 1. Eachpipetting unit (702) comprises two frames (703, 704). In thenon-limiting example shown in FIG. 1, any one of the pipetting unit(702) comprises an electronic module (705). The electronic module (705)of pipetting unit (702 a) is mounted in the lower frame (703), theelectronic module (705) of pipetting unit (702 b) is mounted in theupper frame (704). The Y-axis actuators (717) are also mounted on thepipette units in a staggered fashion. The pipetting units also compriseinterfaces (706) for interacting with pipette tips (3, 4).

FIG. 2 shows the two units (702 a, b) as they are moved together,bringing the two pipette tips (3, 4) into close proximity. Correspondingmodules (e.g., 705) are arranged in a non-overlapping way to allow foran optimal spacing between the two pipetting units. FIG. 3 a) shows adevice (700) with five pipette units (702 a to e) with the staggeredmount of different modules (705). Four of the pipette units (702 b to e)are shown with a short distance between each other. The fifth unit (702a) is shown in a position further away. FIG. 3 b) shows a device (700)with eight pipetting units (702), wherein all units (702) are in closeproximity to the adjacent units (702) and have needles (80) forpipetting.

FIG. 4 shows an embodiment of a pipetting device (700) which is onlymoved in Z-direction. a) Two units (702) are fixed in the support (707).To obtain a sufficiently small raster, e.g. a 9 mm raster, the units(702) are mounted in a staggered manner. Modules (710) on the tools(709) as well as modules (705, 711) on the frame part (703, 704) of thepipette unit (702) are staggered to obtain the required distance betweenthe pipette units (702). b) Shows the pipette units (709 a, b) and theframes (703, 704) in a disassembled manner.

FIG. 5 shows the interface to the frame body (701): a) the frame body isa Y-carriage; the pipetting unit (702) comprises an interacting part(712) which can be engaged with a receiving part (713) of the frame body(701) and releasably fixed. b) Shows a detail of the interacting partbefore engagement. c) Shows the frame engaged to the frame body.

FIG. 6 a) shows an adaptor plate (714) for fixing the pipette tool (709)to the frame part (710) of the pipette unit (702). Other tools (715,716) may also be attached to said frame part (710). b) Shows a detail ofthe pipette tool (709) fixed to the frame part (702).

The pipette unit may comprise additional modules. Preferably, suchmodules comprise sensors. Several types of sensors and other modules areshown in FIG. 7 a) to c), e.g., a magnet (720), a hallsensor (721), aninit-sensor (723) of the Z-drive (718), an init sensor (722) of theY-drive (717), an ultrasound sensor (724).

While the foregoing invention has been described in some detail forpurposes of clarity and understanding, it will be clear to one skilledin the art from a reading of this disclosure that various changes inform and detail can be made without departing from the true scope of theinvention. For example, all the techniques and apparatus described abovecan be used in various combinations. All publications, patents, patentapplications, and/or other documents cited in this application areincorporated by reference in their entirety for all purposes to the sameextent as if each individual publication, patent, patent application,and/or other document were individually indicated to be incorporated byreference for all purposes.

What is claimed:
 1. A method of pipetting samples from a first set ofvessels holding said samples to a second set of vessels, wherein adistance between adjacent vessels of the first set of vessels isdifferent from a distance between adjacent vessels of the second set ofvessels, said method comprising: aspirating said samples from the firstset of vessels with pipette tips mounted on a device for aspirating anddispensing more than one liquid sample, said device comprising: a mainbody comprising a receiving part, two or more adjacent pipetting unitsextending vertically parallel to each other, each of said pipettingunits comprising: an interacting part releasably engaging the receivingpart of the main body in a fixed position; a pipette tip; an interfacefor interacting with an interface of the pipette tip; and an upper frameand a lower frame each configured to receive and mount a module, atleast one module present in the upper or lower frame of each pipettingunit, wherein the modules of two adjacent pipetting units are mounted ina staggered fashion between the upper frame of one of the two or moreadjacent pipetting units, and the lower frame of a second adjacentpipetting unit, said modules comprising at least one of: a pump foraspirating and dispensing a liquid, a Y-axis actuator, and a Z-axisactuator, wherein said Y-axis actuator and said Z-axis actuator functionindependently, or an electronic module for controlling functions of saidpipetting unit; and an X-transfer mechanism connected to said main bodyto which said two or more adjacent pipetting units are connected,wherein a distance between said two or more adjacent pipetting units isadjusted to the distance between said first set of vessels by moving thepipetting units along one axis prior to aspirating said samples from thefirst set of vessels; and dispensing said aspirated samples into thesecond set of vessels after adjusting the distance between the two ormore adjacent pipette units to the distance between said second set ofvessels.
 2. The method of claim 1, wherein said first set of vesselscomprises at least two vessels in a linear arrangement.
 3. The method ofclaim 1, wherein said second set of vessels are integrally formed. 4.The method of claim 1, wherein said second set of vessels comprises amultiwell plate.